Department of Endocrinology, Diabetes and Nutrition, Charite-University Medicine Berlin, Campus Benjamin Franklin, Berlin, Germany.
Metabolism. 2012 Jan;61(1):108-16. doi: 10.1016/j.metabol.2011.05.018. Epub 2011 Jul 7.
The ratio of unsaturated to saturated long-chain fatty acids (LC-FAs) in skeletal muscle has been associated with insulin resistance. Some animal data suggest a modulatory effect of peroxisome proliferator receptor γ (PPARγ) stimulation on stearoyl-CoA desaturase 1 (SCD1) and LC-FA composition in skeletal muscle, but human data are rare. We here investigate whether treatment with a PPARγ agonist affects myocellular SCD1 expression and modulates the intramyocellular fatty acid profile in individuals with impaired glucose tolerance. Muscle biopsies and hyperinsulinemic-euglycemic clamps were performed in 7 men before and after 8 weeks of rosiglitazone treatment. Intramyocellular saturated, monounsaturated, and polyunsaturated intramuscular fatty acid profiles were measured by gas chromatography. Effects on SCD1 messenger RNA expression were analyzed in C2C12 cells and in human biopsies before and after rosiglitazone treatment. As expected, treatment with the PPARγ activator rosiglitazone improved insulin sensitivity in humans. Myocellular SCD1 messenger RNA expression was increased in human biopsies and C2C12 cells. Although the total content of myocellular LC-FA was unchanged, a relative shift from saturated LC-FAs to unsaturated LC-FAs was observed in human biopsies. Particularly, the amount of stearate was reduced, whereas the amounts of palmitoleate as well as oleate and vaccenate were increased, after rosiglitazone therapy. These changes resulted in an increased fatty acid Δ9-desaturation index (16:1/16:0 and 18:1/18:0) in skeletal muscle and a decreased elongase activity index (18:0/16:0). The PPARγ associated phenotypes may be partially explained by an increased Δ9-desaturation and a decreased elongase activity of skeletal muscle.
骨骼肌中不饱和长链脂肪酸（LC-FA）与胰岛素抵抗有关。一些动物数据表明，过氧化物酶体增殖物激活受体γ（PPARγ）刺激对骨骼肌中硬脂酰辅酶 A 去饱和酶 1（SCD1）和 LC-FA 组成具有调节作用，但人体数据很少。我们在此研究了 PPARγ 激动剂治疗是否会影响肌细胞 SCD1 的表达，并调节葡萄糖耐量受损个体的肌内脂肪酸谱。在罗格列酮治疗 8 周前后，对 7 名男性进行了肌肉活检和高胰岛素-正常血糖钳夹。通过气相色谱法测量肌内饱和、单不饱和和多不饱和肌内脂肪酸谱。在 C2C12 细胞和罗格列酮治疗前后的人体活检中分析了对 SCD1 信使 RNA 表达的影响。如预期的那样，PPARγ 激活剂罗格列酮改善了人体的胰岛素敏感性。肌细胞 SCD1 信使 RNA 表达在人体活检和 C2C12 细胞中增加。尽管肌内 LC-FA 的总量不变，但在人体活检中观察到从饱和 LC-FA 到不饱和 LC-FA 的相对转移。特别是，硬脂酸的量减少，而棕榈油酸以及油酸和壬酸的量增加，在罗格列酮治疗后。这些变化导致骨骼肌中的脂肪酸 Δ9-去饱和指数（16:1/16:0 和 18:1/18:0）增加，而延长酶活性指数（18:0/16:0）降低。PPARγ 相关表型可能部分解释为骨骼肌中 Δ9-去饱和增加和延长酶活性降低。
